Exposure to transforming growth factor-β1 after basic fibroblast growth factor promotes the fibroblastic differentiation of human periodontal ligament stem/progenitor cell lines

Abstract

Basic fibroblast growth factor (bFGF) is a cytokine that promotes the regeneration of the periodontium, the specialized tissues supporting the teeth. bFGF, does not, however, induce the synthesis of smooth muscle actin alpha 2 (ACTA2), type I collagen (COL1), or COL3, which are principal molecules in periodontal ligament (PDL) tissue, a component of the periodontium. We have suggested the feasibility of using transforming growth factor-β1 (TGFβ1) to induce fibroblastic differentiation of PDL stem/progenitor cells (PDLSCs). Here, we investigated the effect of the subsequent application of TGFβ1 after bFGF (bFGF/TGFβ1) on the differentiation of PDLSCs into fibroblastic cells. We first confirmed the expression of bFGF and TGFβ1 in rat PDL tissue and primary human PDL cells. Receptors for both bFGF and TGFβ1 were expressed in the human PDLSC lines 1-11 and 1-17. Exposure to bFGF for 2 days promoted vascular endothelial growth factor gene and protein expression in both cell lines and down-regulated the expression of ACTA2, COL1, and COL3 mRNA in both cell lines and the gene fibrillin 1 (FBN1) in cell line 1-11 alone. Furthermore, bFGF stimulated cell proliferation of these cell lines and significantly increased the number of cells in phase G2/M in the cell lines. Exposure to TGFβ1 for 2 days induced gene expression of ACTA2 and COL1 in both cell lines and FBN1 in cell line 1-11 alone. BFGF/TGFβ1 treatment significantly up-regulated ACTA2, COL1, and FBN1 expression as compared with the group treated with bFGF alone or the untreated control. This method might thus be useful for accelerating the generation and regeneration of functional periodontium.

Sequential application of bFGF and BMP‐2 facilitates osteogenic differentiation of human periodontal ligament stem cells

“…bFGF can promote the proliferation of cartilage and PDL cells and has been confirmed to possess high regenerative capacity in treating periodontal disease in a clinical study . Previous studies demonstrated that bFGF promoted the proliferation of PDL cells, as well as increased the cell number of PDLSCs in phase G2/M without an effect on cell viability . In the present study, we confirmed that bFGF dose‐dependently promoted PDLSCs proliferation while high concentration inhibited cell proliferation, which was consistent with the previous studies .…”

Mechanical induction of interleukin‐11 regulates osteoblastic/cementoblastic differentiation of human periodontal ligament stem/progenitor cells

“…We have reported that stretch loading up‐regulates the expression of TGF‐β1 in PDL cells and that TGF‐β1 is localized in functional PDL tissues loaded by continual occlusion . In addition, we also revealed that TGF‐β1 facilitated fibroblastic differentiation of cell line 1‐17 . Thus, TGF‐β1 may be a candidate factor involved in regulating the function of IL‐11 and in maintaining nonmineralized PDL tissues.…”

Effects of short-term inflammatory and/or hypoxic pretreatments on periodontal ligament stem cells: in vitro and in vivo studies

“…Many attempts have now been made to improve cell behavior during ex vivo expansion and to enhance the clinical success of stem cell-based therapies (Kono et al 2013;Proksch et al 2014;Teramatsu et al 2014). Of the various available strategies, short-term pretreatment of cells with pharmaceuticals, such as cytokines, antiapoptotic molecules and growth factors, or the incubation of cells under particular conditions, such as hypoxic environments, appears to be a simple, practical and safe method to maintain, if not strengthen, the therapeutic potential of ex vivo-manipulated cell materials (Peng et al 2013;Lee et al 2015).…”